Assay discrepancies using human coagulation factor VIII chromogenic kits: Results from a plasma-derived factor VIII collaborative study (BSP112).

Chromogenic assay discrepancies were reported at General European Official Medicines Control Laboratories Network (GEON) meetings by laboratories testing FVIII-products. The objectives of the present investigation were to carry out a controlled collaborative study to examine these reports and to delineate the reasons for these discrepancies by assessing affected and unaffected FVIII products. The laboratories followed a strict study protocol, which included assessing their own individual observed factor X (FX) activation times, i.

Peripapillary and optic nerve head vessel density of glaucoma and healthy subjects from Afro-Caribbean and European descent: A pilot study.

Purpose: To compare the peripapillary and optic nerve head vessel density (PP-ONH VD) between glaucoma patients (all, early, moderated, and advanced) and healthy subjects of Afro-Caribbean descent (AD) and European descent (ED).

Methods: This was a cross-sectional study. One eye was evaluated in 90 subjects, including 66 glaucoma patients and 24 healthy subjects, who underwent PP-ONH VD imaging using SPECTRALIS® Optical Coherence Tomography Angiography (OCT-A).

Phacoemulsification combined with micropulse cyclodiode laser in glaucoma patients: efficacy and safety.

Objective: To evaluate the safety and efficacy of phacoemulsification combined with Micropulse transscleral cyclophotocoagulation (MP-TSCPC) in glaucoma patients.

Methods: This is a retrospective case-note review. The participants were adult patients with diagnoses of glaucoma and cataract who required a further reduction in IOP or a reduction in the number of glaucoma drops.

Effect of high-intensity focused ultrasound (HiFU) treatment on intraocular pressure and aqueous humour dynamics: 12 -months results.

Purpose: High intensity focused ultrasound (HiFU) is a cyclodestructive therapy for controlling intraocular pressure (IOP) in glaucoma. The mechanism of action is thought to be through destruction of the ciliary epithelium as well as increased uveoscleral outflow. We reviewed the change in aqueous humour dynamics parameters including aqueous humour flow rate, tonographic outflow facility (TOF) and uveoscleral outflow at 12 months.

Production and characterisation of a candidate hyper-immune serum for the replacement of the Bordetella pertussis mouse antiserum Biological Reference Preparation.

For acellular pertussis (aP) vaccines, the current European Pharmacopoeia (Ph. Eur.) monograph Pertussis vaccine (acellular, component, adsorbed) (1356) requires an immunogenicity assay in mice or guinea pigs to assess the potency of each lot of vaccine (Ph.

Collaborative study for the validation of cell line assays for in-process toxicity and antigenicity testing of Clostridium septicum vaccine antigens - Part 1.

Large numbers of mice are used in testing during the production of Clostridial vaccines. Previous work has indicated that cell line assays could replace mouse tests for certain aspects of this testing. Replacement assays have been developed for the testing of the toxins and toxoids of several clostridial species but none of these assays have been assessed in an international collaborative study.

Intraocular pressure changes following topical ocular hypotensive medications washout.

Background: To review the changes in intraocular pressure (IOP) following topical hypotensive medications washout in patients with primary open angle glaucoma (POAG), ocular hypertension (OHT) and uveitic glaucoma (UG)/OHT.

Methods: The study included 120 patients with POAG, OHT and UG recruited from prospective clinical trials between February 2013 and July 2017. We excluded 20 eyes with IOP of ≤21 mm Hg, 11 eyes with previous incisional surgery and 17 eyes with incomplete data.

Predictors of selective laser trabeculoplasty success in open angle glaucoma or ocular hypertension: does baseline tonography have a predictive role?

Background: The determinants of success of selective laser trabeculoplasty (SLT) in treatment-naïve patients with open angle glaucoma (OAG) and ocular hypertension (OHT) have not been understood fully. Therefore, we have conducted this study to explore the predictors of success.

Methods: This is a retrospective review of a pre-existing database of patients who had received primary SLT at St Thomas' Hospital, London, UK.

Establishment of an erythropoietin CRS with stable measurable dimer content for SEC system suitability qualification.

The European Pharmacopoeia (Ph. Eur.) monograph 1316 'Erythropoietin concentrated solution' prescribes that the dimer content of therapeutic erythropoietin (EPO) preparations must not exceed 2% as determined by Size-Exclusion Chromatography (SEC).

Assessment of UV spectrophotometry for determination of plasmid DNA concentration in vector preparations for human gene therapy products.

The European Pharmacopoeia (Ph. Eur.) general chapter 5.

Validation of ELISA methods for quantification of the major birch allergen Bet v 1 (BSP090).

To date, the potency of allergen products in Europe is expressed in manufacturer-specific units relative to a product-specific in-house reference. Consequently, cross-product comparability of allergen products from different manufacturers with respect to strength and efficacy is impossible. The Biological Standardisation Programme (BSP) project BSP090 addresses this issue via the establishment of reference standards in conjunction with ELISA methods for the quantification of major allergens in allergen products.

Establishment of the Ph. Eur. Hepatitis A virus RNA for NAT testing BRP batch 1.

Detection of viral contamination in plasma donations is critical to prevent transmission of infectious diseases. The European Pharmacopoeia (Ph. Eur.

Collaborative study on saccharide quantification of the type b component in liquid vaccine presentations.

Before release onto the market, it must be demonstrated that the total and free polysaccharide (poly ribosyl-ribitol-phosphate, PRP) content of type b (Hib) vaccine complies with requirements. However, manufacturers use different methods to assay PRP content: a national control laboratory must establish and validate the relevant manufacturer methodology before using it to determine PRP content. An international study was organised by the World Health Organization (WHO), in collaboration with the Biological Standardisation Programme (BSP) of the Council of Europe/European Directorate for the Quality of Medicines & HealthCare (EDQM) and of the European Union Commission, to verify the suitability of a single method for determining PRP content in liquid pentavalent vaccines (DTwP-HepB-Hib) containing a whole-cell pertussis component.

Calibration of the Ph. Eur. human coagulation Factor VIII concentrate BRP batch 5.

The European Pharmacopoeia Biological Reference Preparation (Ph. Eur. BRP) for Factor VIII Concentrate batch 5 was established through a collaborative study involving 14 laboratories organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe) to be used as working standard for potency determination of human coagulation Factor VIII (FVIII) preparations.

Collaborative study for the calibration of replacement batches for the heparin low-molecular-mass for assay biological reference preparation.

The European Pharmacopoeia (Ph. Eur.) prescribes the control of the activity of low molecular mass heparins by assays for anti-Xa and anti-IIa activities (monograph 0828), using a reference standard calibrated in International Units (IU).

Collaborative study for the validation of an improved HPLC assay for recombinant IFN-alfa-2.

The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2 include a nonspecific photometric protein assay using albumin as calibrator and a highly variable cell-based assay for the potency determination of the protective effects.

Transferability study of CHO cell clustering assays for monitoring of pertussis toxin activity in acellular pertussis vaccines.

Current regulations for acellular pertussis (aP) vaccines require that they are tested for the presence of residual or reversion-derived pertussis toxin (PTx) activity using the mouse histamine sensitisation test (HIST). Although a CHO cell clustering assay can be used by manufacturers to verify if sufficient inactivation of the substance has occurred in-process, this assay cannot be used at present for the final product due to the presence of aluminium adjuvants which interfere with mammalian cell cultures. Recently, 2 modified CHO cell clustering assays which accommodate for the adjuvant effects have been proposed as alternatives to the HIST.

Standardization of allergen products: 3. Validation of candidate European Pharmacopoeia standard methods for quantification of major birch allergen Bet v 1.

Background: The BSP090 project aims at establishing European Pharmacopoeia Reference Substances in combination with the corresponding ELISA methods for the quantification of major allergens in allergen products. Two sandwich ELISAs proved suitable for quantification of Bet v 1, the major birch pollen allergen, in preceding phases of BSP090.

Methods: Two Bet v 1-specific ELISA systems were compared with respect to accuracy and precision in a ring trial including 13 laboratories.

Collaborative study for the establishment of erythropoietin BRP batch 4.

The European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for erythropoietin (EPO) is used as a working standard for potency determination of EPO preparations by in vivo bioassay as prescribed in the Ph.

Establishment of hepatitis A detection antibodies set BRR batch 3 for antigen content determination by ELISA.

The current batch of the European Pharmacopoeia (Ph. Eur.) Biological Reference Reagents (BRRs) used for the in vitro potency assay of hepatitis A vaccines (HAV) by ELISA (enzymelinked immunosorbent assay) was established in 2012 for use in conjunction with Ph.

Collaborative study for the establishment of the 2(nd) International Standard for Bleomycin Complex A2/B2.

Organization (WHO) International Standard (IS) for bleomycin complex A2/B2. Eight laboratories from different countries participated. Potencies of the candidate material were estimated by microbiological assays with sensitive micro-organisms.

Collaborative study for the establishment of the 4(th) International Standard for Streptomycin.

An international collaborative study was organised to establish the 4(th) World Health Organization (WHO) International Standard (IS) for Streptomycin. Fourteen laboratories from different countries participated. Potencies of the candidate material were estimated by microbiological assays with sensitive micro-organisms.

Establishment of the human albumin for electrophoresis Ph. Eur. BRP batches 3 and 4.

Due to the diminished stocks of the 2nd batch of the European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for human albumin for electrophoresis, the European Directorate for the Quality of Medicines & HealthCare (EDQM) initiated in 2014 an international collaborative study for the establishment of two replacement batches.

Establishment of hepatitis A vaccine (inactivated, non-adsorbed) BRP batches 2 and 3.

The current hepatitis A vaccine (HAV), inactivated, non-adsorbed, European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) is used for the in vitro potency assay of HAV as prescribed by the Ph.